Abstract
We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies ('1.5 fold, P '.5) from a discovery cohort of HLA antibody–negative, endothelial cell crossmatch–positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P '.1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P '.1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, '1R) with an area under the curve of 0.87 (P '.05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection.
Original language | English (US) |
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Pages (from-to) | 2768-2780 |
Number of pages | 13 |
Journal | American Journal of Transplantation |
Volume | 20 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2020 |
Keywords
- autoantibody
- autoantigen
- clinical research/practice
- heart transplantation/cardiology
- histocompatibility
- immunogenetics
- microarray/protein array
- organ transplantation in general
- rejection
- translational research/science
ASJC Scopus subject areas
- Immunology and Allergy
- Transplantation
- Pharmacology (medical)